（08.09 --08.15 / 2010）
恒峰g22国际集团:陶国新 

　　本周动态蕴含以下内容：沙门氏菌医治肿瘤可诱发杀灭癌细胞免疫反映；脊髓危险幼鼠成功再生神经通路；发现骨髓中造血干细胞生态龛的重要成员；细胞因子介导的肿瘤免疫疗法；星形胶质细胞可转化为神经细胞
。

1. 沙门氏菌医治肿瘤可诱发杀灭癌细胞免疫反映
【提要】美国科学推进会 2010-8-13 10:43:19
　　一项在幼鼠中的新的钻研汇报说，用沙门氏菌医治肿瘤可诱发一种可能有效杀灭癌细胞的免疫反映
。该发现可援手科学家们创造可注射到病人体内的杀灭肿瘤的免疫细胞，或其能证明对研发一种潜在的抗癌“疫苗”有所援手
。在体内放哨的免疫细胞常？山缙诘陌┫赴鹞斐５南赴，并将其杀灭
。这一过程依赖于衔接蛋白43，这是可在分歧类型的细胞间形成藐幼交统统路（称作间隙衔接）的一种蛋白
。被称作肽的肿瘤蛋白碎片可通过这些通路逃逸并进入到在其表表展示这些肽的免疫细胞之中
。这些肽的作用相当于“红旗警示”，从而触发一种特异性的抗癌免疫反映
。但是随着癌细胞的进展和增殖，它们可令免疫细胞无法对其进行鉴别
。如今，Fabiana Saccheri及其在意大利的同事证明，将沙门氏菌注射到肿瘤之中可令这些肿瘤细胞重新可能被免疫细胞鉴别
。钻研人员发现，被注射的细菌阐扬了一种关键性的职能：它们重新激活了衔接蛋白43，而这种蛋白随着癌细胞的成长常；崾艿揭衷
。在本钻研中，该团队发现，来自幼鼠和人的习染了沙门氏菌的玄色素瘤细胞可增长在这些细胞中的衔接蛋白43的含量
。 其了局是新的间隙衔接形成了，它使得染有黄色荧光的幼分子可能在肿瘤细胞之间通畅或从肿瘤细胞进入免疫细胞
。但是钻研人员但愿查明，这种可使肿瘤肽进入免疫细胞的间隙衔接也会在活体动物中出现
。因而，他们对患癌的幼鼠进行了沙门氏菌的医治并观察到，正如在尝试室的分离细胞中所观察到的，这些肿瘤肽可通过间隙衔接而进入到免疫细胞之中，它们在那里被装载到了细胞的表表
。这些新被激活的免疫细胞忽然可能鉴别并杀灭在幼鼠中的肿瘤细胞
。令人感兴致的是，这种步骤还；び资蟛换岱⑸┲⒗┥⒌缴矶蔚钠渌课，而这正是一种“疫苗接种”大局的预防性战术
。
【点评】
　　通过细菌习染重新激活免疫细胞鉴别和杀灭肿瘤细胞，不失为一种富于设想力的伎俩，而能否有实用价值依然在于该步骤有效性有多强以及使用时的安全性
。即便不能发展成为一种高效的医治癌症的步骤，它还是提供了一种思路，即是否可能将难治性致命疾病通过极度规伎俩转变为容易处置的问题来解决
。

【原文摘录】Sci. Transl. Med. 2, 44ra57 (2010). DOI: 10.1126/scitranslmed.3000739
Bacteria-induced gap junctions in tumors favor antigen cross-presentation and antitumor immunity
F. Saccheri, C. Pozzi, F. Avogadri, S. Barozzi, M. Faretta, P. Fusi, M. Rescigno.
Antigen-presenting dendritic cells (DCs) trigger the activation of cytotoxic CD8 T cells that target and eliminate cells with the antigen on their surface. Although DCs usually pick up and process antigens themselves, they can also receive peptide antigens from other cells via gap junctions. We demonstrate here that infection with Salmonella can induce, in both human and murine melanoma cells, the up-regulation of connexin 43 (Cx43), a ubiquitous protein that forms gap junctions and that is normally lost during melanoma progression. Bacteria-treated melanoma cells can establish functional gap junctions with adjacent DCs. After bacterial infection, these gap junctions transferred preprocessed antigenic peptides from the tumor cells to the DCs, which then presented those peptides on their surface. These peptides activated cytotoxic T cells against the tumor antigen, which could control the growth of distant uninfected tumors. Melanoma cells in which Cx43 had been silenced, when infected in vivo with bacteria, failed to elicit a cytotoxic antitumor response, indicating that this Cx43 mechanism is the principal one used in vivo for the generation of antitumor responses. The Cx43-dependent cross-presentation pathway is more effective than standard protocols of DC loading (peptide, tumor lysates, or apoptotic bodies) for generating DC-based tumor vaccines that both inhibit existing tumors and prevent tumor establishment. In conclusion, we exploited an antimicrobial response present in tumor cells to activate cytotoxic CD8 T cells specific for tumor-generated peptides that could directly recognize and kill tumor cells.

2. 脊髓危险幼鼠成功再生神经通路
【提要】科技日报 2010-8-10 11:59:52
　　近期，钻研人员初次诱导脊髓受损的幼鼠再生出可节造自主行动的神经通路，这一成就有望开发出医治瘫痪和其他活动职能性阻碍的新步骤
。有关论文颁发于《天然•神经科学》杂志
。在对幼鼠的钻研中，美国加州大学欧文分校、加州大学圣地亚哥分校和哈佛大学结合组成的钻研团队通过逆转一个分子通路中的生物钟而获得了这项突破，该分子通路对于皮质脊髓束神经通路而言极度关键
。他们剔除了一种名为PTEN（同源性磷酸酶-张力蛋白）的酶，这种酶节造的分子通路叫做mTOR，是细胞成长的关键调节器
。在发育初期，PTEN的活性很低，细胞增殖不受影响；当发育实现时，PTEN就会关关，抑造mTOR分子通路，细胞也会失去任何再生能力
。“在此之前，如此壮大的神经再生不成能在脊髓中出现，”加州大学欧文分校里夫-欧文钻研中心掌管人、解剖学和神经生物学教授斯图尔特说，“瘫痪和因脊髓危险导致的职能失落一向被以为是无药可医的，但恒峰g22钻研发现指了然一种潜在的医治步骤，即诱导脊髓受伤患者体内的神经通路再生
。”凭据克里斯托弗和丹纳•利夫基金会提供的数据，约莫有2%的美国人因脊髓危险而出现某种大局的瘫痪，这重要是由于衔接大脑和脊髓的神经通路中断导致的
。一粒葡萄大幼的危险就可导致危险面以下的职能全数失落
。好比，颈部的危险可致胳膊和腿瘫痪，肩部以下感知全无，大幼便失禁，性职能失落，以及一系列次级健全风险，蕴含泌尿系统习染，由于无法移动双腿而生出褥疮和血栓等
。斯图尔特说：“若是可能找到一个步骤让这些遭到粉碎的通路再生，所有这些失落的职能都能够复原
。”他和同事们在钻研PTEN缺失疗法能否让脊髓危险的幼鼠复原现实活动职能，并进一步相识最佳的医治功夫，同时试图为该疗法开发一套药物输送系统
。
【点评】
　　通过剔除Pten基因，使脊髓神经细胞回到类似发育初期的状态从而复原再生能力，建复危险的神经通路
。战术很好，只是目前还只在幼鼠试验中观察到神经细胞的再生，能否复原幼鼠的现实活动职能不明显
。并且，若何实现体内脊髓神经细胞的Pten基因剔除或寡言是另一个巨大挑战
。

【原文摘录】Nature Neuroscience doi:10.1038/nn.2603
PTEN deletion enhances the regenerative ability of adult corticospinal neurons
Kai Liu,Yi Lu,Jae K Lee, et al.
Despite the essential role of the corticospinal tract (CST) in controlling voluntary movements, successful regeneration of large numbers of injured CST axons beyond a spinal cord lesion has never been achieved. We found that PTEN/mTOR are critical for controlling the regenerative capacity of mouse corticospinal neurons. After development, the regrowth potential of CST axons was lost and this was accompanied by a downregulation of mTOR activity in corticospinal neurons. Axonal injury further diminished neuronal mTOR activity in these neurons. Forced upregulation of mTOR activity in corticospinal neurons by conditional deletion of Pten, a negative regulator of mTOR, enhanced compensatory sprouting of uninjured CST axons and enabled successful regeneration of a cohort of injured CST axons past a spinal cord lesion. Furthermore, these regenerating CST axons possessed the ability to reform synapses in spinal segments distal to the injury. Thus, modulating neuronal intrinsic PTEN/mTOR activity represents a potential therapeutic strategy for promoting axon regeneration and functional repair after adult spinal cord injury.

3. 发现骨髓中造血干细胞生态龛的重要成员
【提要】
　　在骨髓中形成造血干细胞生态龛的细胞身份一向不明显
。此刻，Paul Frenette及其同事鉴别出，表白巢蛋白nestin的间充质干细胞为形成生态龛的细胞
。这些细胞与造血干细胞有亲昵物理关系，表白高水平的参加干细胞守护的基因，它们的删除会降低造血祖细胞的骨髓归巢职能
。这项工作显示，骨髓中的干细胞生态龛是两种截然分歧的体干细胞类型之间的一种同伴关系
。
【点评】
　　表白巢蛋白的间充质干细胞被发此刻组成造血干细胞的生态龛和守护造血干细胞方面起重要作用
。对于钻研造血干细胞的性命法规和血液病的医治上很可能有积极作用
。

【原文摘录】Nature 466, 829-834 (12 August 2010) | doi:10.1038/nature09262
Mesenchymal and haematopoietic stem cells form a unique bone marrow niche
Simón Méndez-Ferrer, Tatyana V. Michurina, Francesca Ferraro, et al.
The cellular constituents forming the haematopoietic stem cell (HSC) niche in the bone marrow are unclear, with studies implicating osteoblasts, endothelial and perivascular cells. Here we demonstrate that mesenchymal stem cells (MSCs), identified using nestin expression, constitute an essential HSC niche component. Nestin+ MSCs contain all the bone-marrow colony-forming-unit fibroblastic activity and can be propagated as non-adherent ‘mesenspheres’ that can self-renew and expand in serial transplantations. Nestin+ MSCs are spatially associated with HSCs and adrenergic nerve fibres, and highly express HSC maintenance genes. These genes, and others triggering osteoblastic differentiation, are selectively downregulated during enforced HSC mobilization or β3 adrenoreceptor activation. Whereas parathormone administration doubles the number of bone marrow nestin+ cells and favours their osteoblastic differentiation, in vivo nestin+ cell depletion rapidly reduces HSC content in the bone marrow. Purified HSCs home near nestin+ MSCs in the bone marrow of lethally irradiated mice, whereas in vivo nestin+ cell depletion significantly reduces bone marrow homing of haematopoietic progenitors. These results uncover an unprecedented partnership between two distinct somatic stem-cell types and are indicative of a unique niche in the bone marrow made of heterotypic stem-cell pairs.

4. 细胞因子介导的肿瘤免疫疗法
【提要】
　　人体免疫系统成功地进化，能对付很多病原体
。通过接种疫苗，我们可能驾驭和推进免疫反映来扑灭传染病
。只管如此，我们还只是刚刚起头相识肿瘤天然免疫监督机造以及为什么有些情况下恒峰g22免疫系统不能解除肿瘤的成长发育
。本编综述回首了最近在这一领域出现的鼓励人心的钻研了局和不休扩大的有关细胞因子诱导效应以及显示辅助细胞因子医治很有但愿推进抗肿瘤免疫的临床前和临床数据等方面的知识
。
【点评】
　　提供给各人关于肿瘤免疫疗法的一些新进展和新但愿
。

【原文摘录】Trends in Pharmacological Sciences, Volume 31, Issue 8, 356-363
Fighting cancers from within: augmenting tumor immunity with cytokine therapy
Marc Pellegrini, Tak W. Mak, Pamela S. Ohashi
The human immune system has successfully evolved to fight many pathogens. Through vaccination, we can harness and improve immune responses to eradicate infections. Despite this success, we are only now beginning to understand the natural tumor immune surveillance mechanisms and why, in some instances, our immune system fails to abrogate the development and growth of tumors. Encouraging results with the latest immunotherapies have renewed enthusiasm in the field. A central component of these therapies is the contribution of cytokines. Here we review our expanding knowledge of cytokine-induced effects as well as preclinical and clinical data that indicate adjuvant cytokine therapies may hold much promise in improving anti-tumor immunity. Further studies on optimal synergistic combinations, timing, duration and additional adjuvant therapies are required to realize the full potential of cytokines as immunotherapeutic agents.

5. 星形胶质细胞可转化为神经细胞
【提要】起源：《PLoS生物学》 颁布功夫：2010-8-11 9:34:09
　　德国慕尼黑大学、亥姆霍兹慕尼黑中心组成的一个钻研幼组18日颁发在脑细胞再生钻研方面获得新进展：使用特殊的转录因子可使大脑皮层的星形胶质细胞转化为职能性神经细胞
。这一成就将有助于老年痴呆症或中风等疾病的新疗法钻研
。由亥姆霍兹慕尼黑中心干细胞钻研所所长玛格达莱娜•格茨辅导的这个钻研幼组在最新一期美国《公共科学图书馆—生物学》杂志上汇报说，通过钻研证实，在大脑皮层的星形胶质细胞中植入“Neurogenin2”转录因子可使星形胶质细胞转变为兴奋性神经元，在同样的星形胶质细胞中植入“Dlx2”转录因子则可使其转变为抑造性神经元
。
星形胶质细胞是哺乳动物脑内散布最宽泛的一类细胞，其胞体发出的很多长而分支的突起伸展充填在神经细胞的胞体及其突起之间，起支持和分隔神经细胞的作用
。德国钻研人员指出，星形胶质细胞与放射状胶质细胞亲昵有关，而后者则是胎胚发育过程中大无数神经元的先驱细胞
。德钻研人员进一步诠释说，格茨辅导的钻研幼组在几年前的钻研中已发现，在幼鼠大脑皮层正本不拥有形成神经元能力的星形胶质细胞中植入特殊的调节蛋白，可促使其转变为神经元
。而他们的最新钻研则显示，新形成的神经元在特殊转录因子的影响下可进一步形成功能性突触，开释出兴奋性或抑造性的递质
。不仅还在发育的星形胶质细胞发生转变，并且因受损而被激活的成熟大脑中的星形胶质细胞也能发生这种转变
。这一发现使钻研人员相信有望找到用脑中现有的星形胶质细胞“更新”因伤或疾病而受损的脑细胞的步骤
。（起源：新华社　班玮）
【点评】
通过基因技术直接刷新和转变组织细胞类型的例子
。对于体表再生神经细胞的钻研有参考价值，但目前看不出有任何医治上的实用价值
。

【原文摘录】PLoS Biol 8(5): e1000373. doi:10.1371/journal.pbio.1000373
Directing Astroglia from the Cerebral Cortex into Subtype Specific Functional Neurons.
Heinrich C, Blum R, Gascón S, et al.
Astroglia from the postnatal cerebral cortex can be reprogrammed in vitro to generate neurons following forced expression of neurogenic transcription factors, thus opening new avenues towards a potential use of endogenous astroglia for brain repair. However, in previous attempts astroglia-derived neurons failed to establish functional synapses, a severe limitation towards functional neurogenesis. It remained therefore also unknown whether neurons derived from reprogrammed astroglia could be directed towards distinct neuronal subtype identities by selective expression of distinct neurogenic fate determinants. Here we show that strong and persistent expression of neurogenic fate determinants driven by silencing-resistant retroviral vectors instructs astroglia from the postnatal cortex in vitro to mature into fully functional, synapse-forming neurons. Importantly, the neurotransmitter fate choice of astroglia-derived neurons can be controlled by selective expression of distinct neurogenic transcription factors: forced expression of the dorsal telencephalic fate determinant neurogenin-2 (Neurog2) directs cortical astroglia to generate synapse-forming glutamatergic neurons; in contrast, the ventral telencephalic fate determinant Dlx2 induces a GABAergic identity, although the overall efficiency of Dlx2-mediated neuronal reprogramming is much lower compared to Neurog2, suggesting that cortical astroglia possess a higher competence to respond to the dorsal telencephalic fate determinant. Interestingly, however, reprogramming of astroglia towards the generation of GABAergic neurons was greatly facilitated when the astroglial cells were first expanded as neurosphere cells prior to transduction with Dlx2. Importantly, this approach of expansion under neurosphere conditions and subsequent reprogramming with distinct neurogenic transcription factors can also be extended to reactive astroglia isolated from the adult injured cerebral cortex, allowing for the selective generation of glutamatergic or GABAergic neurons. These data provide evidence that cortical astroglia can undergo a conversion across cell lineages by forced expression of a single neurogenic transcription factor, stably generating fully differentiated neurons. Moreover, neuronal reprogramming of astroglia is not restricted to postnatal stages but can also be achieved from terminally differentiated astroglia of the adult cerebral cortex following injury-induced reactivation.